This proposal will explore whether rats may represent a small animal model for HIV replication. The principal investigator presents evidence that transgenic rat cells expressing human CD4 and HIV co-receptor supported replication at a similar level to that in human cells. Primary rat lymphocytes were also able to support HIV Tat transactivation of viral transcription suggesting that the block to these steps that exists in mouse cells do not exist in rat cells. The investigator proposes to develop transgenic rats expressing human CD4 and an HIV co-receptor. The study will evaluate animals for the permissivity to HIV replication and pathogenesis.